Curcumin-Mediated Apoptotic Cell Death in Papillary Thyroid Cancer and Cancer Stem-Like Cells through Targeting of the JAK/STAT3 Signaling Pathway.
Apoptosis
/ drug effects
Cell Line, Tumor
Cell Movement
/ drug effects
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Cisplatin
/ pharmacology
Curcumin
/ pharmacology
Drug Synergism
Humans
Interleukin-6
/ metabolism
Janus Kinases
/ metabolism
Neoplastic Stem Cells
/ drug effects
Reactive Oxygen Species
/ metabolism
STAT3 Transcription Factor
/ metabolism
Signal Transduction
/ drug effects
Thyroid Cancer, Papillary
/ metabolism
Thyroid Neoplasms
/ metabolism
Up-Regulation
/ drug effects
STAT3
apoptosis
cancer stem cells
cell proliferation
cisplatin
curcumin
thyroid cancer
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
09 Jan 2020
09 Jan 2020
Historique:
received:
12
12
2019
revised:
31
12
2019
accepted:
06
01
2020
entrez:
16
1
2020
pubmed:
16
1
2020
medline:
2
10
2020
Statut:
epublish
Résumé
The constitutive activation of Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signal transduction is well elucidated in STAT3-mediated oncogenesis related to thyroid cancer and is considered to be a plausible therapeutic target. Hence, we investigated whether curcumin, a natural compound, can target the JAK/STAT3 signaling pathway to induce cytotoxic effects in papillary thyroid cancer (PTC) cell lines (BCPAP and TPC-1) and derived thyroid cancer stem-like cells (thyrospheres). Curcumin suppressed PTC cell survival in a dose-dependent manner via the induction of caspase-mediated apoptosis and caused the attenuation of constitutively active STAT3 (the dephosphorylation of Tyr705-STAT3) without affecting STAT3. Gene silencing with STAT3-specific siRNA showed the modulation of genes associated with cell growth and proliferation. The cotreatment of PTC cell lines with curcumin and cisplatin synergistically potentiated cytotoxic effects via the suppression of JAK/STAT3 activity along with the inhibition of antiapoptotic genes and the induction of proapoptotic genes, and it also suppressed the migration of PTC cells by downregulating matrix metalloproteinases and the inhibition of colony formation. Finally, thyrospheres treated with curcumin and cisplatin showed suppressed STAT3 phosphorylation, a reduced formation of thyrospheres, and the downregulated expression of stemness markers, in addition to apoptosis. The current study's findings suggest that curcumin synergistically enhances the anticancer activity of cisplatin in PTC cells as well as in cancer stem-like cells by targeting STAT3, which suggests that curcumin combined with chemotherapeutic agents may provide better therapeutic outcomes.
Identifiants
pubmed: 31936675
pii: ijms21020438
doi: 10.3390/ijms21020438
pmc: PMC7014270
pii:
doi:
Substances chimiques
Interleukin-6
0
Reactive Oxygen Species
0
STAT3 Transcription Factor
0
STAT3 protein, human
0
Janus Kinases
EC 2.7.10.2
Curcumin
IT942ZTH98
Cisplatin
Q20Q21Q62J
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Medical Research Center
ID : RP # 16354/16
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest.
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